Regulatory frameshifting in antizyme mRNA is a central event for maintaining polyamine homeostasis.
A, schematic representation of the role of the negative regulator, antizyme, in maintaining polyamine homeostasis. Ornithine decarboxylase (ODC) catalyzes the first and rate-limiting step in the polyamine synthesis. Antizyme disrupts the active ornithine decarboxylase homodimer and targets it for ubiquitin independent degradation by the 26S proteasome. Antizyme also regulates the polyamine membrane transporter by inhibiting polyamine uptake and stimulating polyamine excretion. Antizyme protein synthesis requires translational frameshifting, which is stimulated by free intracellular polyamines. This event completes an autoregulatory circuit. B, C. cinerea antizyme mRNA sequence in the vicinity of the frameshift site.